Elsevier

European Journal of Cancer

Volume 41, Issue 17, November 2005, Pages 2645-2654
European Journal of Cancer

Inflammation and prognosis in colorectal cancer

https://doi.org/10.1016/j.ejca.2005.07.017Get rights and content

Abstract

Aim of the study

Previous work has indicated that quantification of inflammatory cell reaction is of prognostic value in colorectal cancer. We evaluated the prognostic significance of inflammatory cell reaction patterns in colorectal cancer and developed a grading method which could be used in the routine assessment of tumours.

Methods

The intensity of overall inflammatory cell reaction, numbers of neutrophilic and eosinophilic granulocytes, lymphoid cells and macrophages in both the central region and the invasive margin were estimated in 386 colorectal cancer patients. Prognostic significance was analysed by uni- and multivariate analysis.

Results

Our method for classification of inflammatory reaction was reliable. High-grade inflammation at the invasive margin in Dukes’ stage A and B cancers (pT1-2N0 and pT3N0, respectively) was associated with better 5-year-survival (87.6%) than low-grade inflammation (47.0%).

Conclusions

Inflammatory cell response at the invasive border is a relevant prognostic indicator and could be easily incorporated into the routine evaluation of histopathological specimens.

Introduction

Colorectal cancer is the second most common cause of cancer-related death and its incidence is increasing in many Western countries. Over one third of the patients with colorectal cancer will die within five years after diagnosis, and most of fatal outcomes result from liver metastases.

Patients with metastatic colorectal carcinoma benefit from adjuvant chemotherapy 1, 2, but it is controversial whether chemotherapy should be offered to patients with Dukes’stage B (pT3N0) colorectal cancer 3, 4. One third to one fourth of the patients with Dukes’ stage B colorectal cancer die of the disease despite complete resection of the primary tumour. Numerous reports have focused on ancillary techniques that could be used to determine which Dukes’ stage B patients have a poor prognosis, but none of the methods have entered general use so far. To date, the rationale behind the utilization of adjuvant therapy depends largely on the findings given in the pathology report, including WHO histological grade and tumour stage according to pTNM, Astler–Coller or the Turnbull modification of Dukes’ classification (see Table 1) 5, 6.

The presence of inflammatory cells in human malignant tumours is a common phenomenon. Inflammatory cell reaction within the tumour and at the invasive margin is thought to be a manifestation of the immune response against cancer cells and cancer-associated apoptosis 7, 8. The influence of immune response on the behaviour of colorectal carcinomas has already been established previously. For example, the predictive value of inflammatory cell reaction is a part of the Jass classification [9]. Other prognostic immune-related alterations include the so-called Crohn’s-like reaction [10]. There is limited experience of the use of these factors as prognostic indicators. In most studies they have not proven to be better than previous classification systems, hence they are not widely included in routine pathology reports.

New prognostic markers for colorectal cancer, which could be included in routine pathological analysis, are needed to determine optimal therapy. The aim of the present study was to utilize an easy-to-use grading scheme for assessment of the inflammatory reaction, and evaluate the prognostic significance of inflammatory cell reaction in colorectal cancer. In addition to overall prognostic analysis, we focused on the discriminating value of inflammatory cell reaction in Dukes’ A and B cancers.

Section snippets

Materials and methods

The study material consists of a consecutive series of 466 colorectal carcinoma patients operated in Oulu University Hospital between January 1986 and December 1996. Complete follow-up data could be obtained in 386 patients who were included in the study. The patients were followed up for 60 months or until their death (mean 41 months). Medical histories and clinical details were reviewed from the case records and the outcome of the patients from the cancer registry files (Finnish Cancer

Inflammatory cells in tumour bulk and invasive margin

We were able to evaluate the invading margin (Fig. 1, Fig. 2) in 374 cases out of 386 cases (96.9%). In 12 cases the invasive margin was not included in the sections, and these were excluded from further analysis. The mean age of all patients was 67 (SD 13; range 12–93) years. The distribution of Dukes’ stage, WHO grading and tumour location in relation to 5-year survival is presented in Table 2. There were no differences between males (N = 179) and females in any of these features (data not

Discussion

An inflammatory reaction is frequently observed in various cancers, and depending on the cancer type, it has been shown to have either a positive or negative influence on survival. In this study, we developed a simple and reproducible grading scheme for estimation of inflammatory reaction at the invasive margin and analysed the prognostic significance of our classification in a large series of patients with colorectal cancer. We were able to show that high-grade inflammation has an independent

Conflict of interest statement

None declared.

Acknowledgements

The authors wish to thank Mr. Risto Bloigu, M.Sc., for advise in statistical methods, and Mr. Martin Pike, MBBCh, for the preparation of English language. This study was supported by the Northern Ostrobothnia Hospital District, Finland.

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